crossing96/oncoscreening huggingface dataset:
Prospective Evaluation of Health-Related Quality of Life in Patients with Metastatic Urothelial Carcinoma Undergoing Immunotherapy with Pembrolizumab: Symptom Burden Can Predict Survival.	INTRODUCTION: Despite the fact that guidelines recommend monitoring of quality of life during all phases of treatment in urothelial carcinoma, prospective data about health-related quality of life (HRQoL) in metastatic urothelial carcinoma undergoing immunotherapy are sparse. Consequently, we performed a prospective clinical pilot study about HRQoL using the Functional Assessment of Cancer Therapy - Immune Checkpoint Modulator (FACT-ICM) questionnaire. MATERIALS AND METHODS: Formally, this study is a prospective uni-centric noninterventional observation from January 2021 to December 2021. RESULTS: Fourteen patients with a mean age of 73.9 years (SD 8.8) participated in the study. The physical well-being subscale of FACT-G is most impaired during therapy with mean scores of 7.5, 6.2, and 4.0 followed by the emotional well-being. The FACT-G total score is stable during therapy with mean scores of 51.1, 50.4, and 48.0 and it is not significantly decreasing during therapy (p = 0.317). Furthermore, the symptom burden of these patients is low and not significantly changing over time (p = 0.500), but survival decreases significantly if symptom burden is high (FACT-ICM score over 40; p < 0.001). CONCLUSION: Physical and emotional needs have a strong impact on HRQoL and should be dealt with during treatment. If symptom burden is high, survival decreases. This needs further evaluation.	bladder
The osteoclast-type giant cell rich carcinoma of urinary bladder: A case series.	BACKGROUND: Osteoclast-type giant cell-rich carcinomas (OGCRCs) of urinary bladder are extremely rare, aggressive tumors that are often diagnosed as undifferentiated carcinomas. The morphology overlaps with other giant cell-rich benign and malignant bladder lesions. Little is known about the pathogenesis and clinical management of this aggressive variant. The aim of this study was to review clinico-pathologic features, and survival characteristics in a series of OGCRCs. MATERIALS AND METHODS: Five cases of OGCRCs of bladder were retrospectively reviewed. Clinical presentation, histomorphology, ancillary tests, treatment and follow-up data were retrieved and analyzed. RESULTS: All patients were adult males (age range 63-86 years) and presented with painless gross hematuria. All cases showed biphasic morphology with polygonal to epithelioid to spindle mononuclear cells (MCs) and scattered multinucleated osteoclast-like giant cells (OGCs). Background urothelium showed urothelial carcinoma in-situ (CIS) (4/5) and/or invasive urothelial carcinoma (UC) (2/5) and invasive high-grade papillary urothelial carcinoma (PUC) (2/5). MCs showed focal expression of at least one epithelial marker and focal/diffuse expression of urothelial markers. OGCs were positive only for histiocytic markers. Oncomine test showed presence of p53 mutation (p.R282W) in case 3. Pathologic stage was T1 (n = 3), T2b (n = 1) and T3a (n = 1). 2/5 patients died of disease within 3 years of diagnosis. CONCLUSIONS: OGCRC is an extremely rare and potentially aggressive malignant neoplasm of bladder. Most cases have associated conventional in-situ or invasive UC supporting undifferentiated or de-differentiated nature of this neoplasm. Surgery should be considered given the potential for aggressive behavior. However optimal treatment for OGCRCs remains unknown.	bladder
FORT-1: Phase II/III Study of Rogaratinib Versus Chemotherapy in Patients With Locally Advanced or Metastatic Urothelial Carcinoma Selected Based on FGFR1/3 mRNA Expression.	PURPOSE: Rogaratinib, an oral pan-fibroblast growth factor receptor (FGFR1-4) inhibitor, showed promising phase I efficacy and safety in patients with advanced urothelial carcinoma (UC) with FGFR1-3 mRNA overexpression. We assessed rogaratinib efficacy and safety versus chemotherapy in patients with FGFR mRNA-positive advanced/metastatic UC previously treated with platinum chemotherapy. METHODS: FORT-1 (ClinicalTrials.gov identifier: NCT03410693) was a phase II/III, randomized, open-label trial. Patients with FGFR1/3 mRNA-positive locally advanced or metastatic UC with ≥ 1 prior platinum-containing regimen were randomly assigned (1:1) to rogaratinib (800 mg orally twice daily, 3-week cycles; n = 87) or chemotherapy (docetaxel 75 mg/m(2), paclitaxel 175 mg/m(2), or vinflunine 320 mg/m(2) intravenously once every 3 weeks; n = 88). The primary end point was overall survival, with objective response rate (ORR) analysis planned following phase II accrual. Because of comparable efficacy between treatments, enrollment was stopped before progression to phase III; a full interim analysis of phase II was completed. RESULTS: ORRs were 20.7% (rogaratinib, 18/87; 95% CI, 12.7 to 30.7) and 19.3% (chemotherapy, 17/88; 95% CI, 11.7 to 29.1). Median overall survival was 8.3 months (95% CI, 6.5 to not estimable) and 9.8 months (95% CI, 6.8 to not estimable; hazard ratio, 1.11; 95% CI, 0.71 to 1.72; P = .67). Grade 3/4 events occurred in 37 (43.0%)/4 (4.7%) patients and 32 (39.0%)/15 (18.3%), respectively. No rogaratinib-related deaths occurred. Exploratory analysis of patients with FGFR3 DNA alterations showed ORRs of 52.4% (11/21; 95% CI, 29.8 to 74.3) for rogaratinib and 26.7% (4/15; 95% CI, 7.8 to 55.1) for chemotherapy. CONCLUSION: To our knowledge, these are the first data to compare FGFR-directed therapy with chemotherapy in patients with FGFR-altered UC, showing comparable efficacy and manageable safety. Exploratory testing suggested FGFR3 DNA alterations in association with FGFR1/3 mRNA overexpression may be better predictors of rogaratinib response.	bladder
HOXA1 promotes proliferation and metastasis of bladder cancer by enhancing SMAD3 transcription.	BACKGROUND: Recent studies showed that HOXA1 can promote or suppress the transcription of target genes via binding to their promoter region, therefore regulating the development and progression of various cancers. However, the biological function of HOXA1 in bladder cancer (Bca) remains unknown. METHODS: qRT-PCR and Western blot assay was performed to measure the mRNA protein level of HOXA1 in Bca cells. CCK-8 and cell colony formation assay were carried out to detect cell proliferation ability. Wound healing assay was applied to detect cell migration ability, while transwell assay was applied to detect cell invasion ability. Chromatin Immunoprecipitation (ChIP) and dual-luciferase reporter assay were used to investigate the molecular mechanisms underlying HOXA1. RESULTS: In this study, we discovered that HOXA1 mRNA and protein was dramatically increased in Bca tissues and cells compared to matched normal tissues and normal bladder epithelial cell. Enhanced HOXA1 expression was positively correlated with bigger tumor size and lymphatic metastasis, causing shorter overall survival to Bca patients. Knockdown of HOXA1 obviously impaired cell proliferation and metastasis ability. Further experiments proved that HOXA1 could strength the transcription of SMAD3 via binding to the promoter region of SMAD3. CONCLUSION: In conclusion, our study suggested that HOXA1 contributed to the growth and metastasis of Bca and it might serve as a tumor biomarker for Bca treatment and prognosis monitoring.	bladder
SENP3 affects the expression of PYCR1 to promote bladder cancer proliferation and EMT transformation by deSUMOylation of STAT3.	Abnormal activation of signal transducer and activator of transcription 3 (STAT3) has been found in various types of human cancers, including bladder cancer (BC). In our study, we examined the regulation of STAT3 post-translational modifications (PTMs) and found that SENP3 is high in bladder cancer. Sentrin/SUMO-specific protease3 (SENP3) and STAT3 were highly expressed in BC tissues when compared with tissue adjacent to carcinoma. SENP3 induced STAT3 protein level and p-STAT3 translocating into nuclear through deSUMOylation of STAT3. Further, nuclear STAT3, as a transcriptional activity factor, promoted pyrroline-5-carboxylate reductase 1 PYCR1 gene and protein level by interacting with the promoter of (PYCR1). Next, we found that knockdown of PYCR1 inhibited Epithelial to mesenchymal transition of bladder cancer, and simultaneously mitigated the carcinogenic effects of STAT3. In vitro, STAT3 knockdown in bladder cancer cells inhibited cell proliferation, migration, and invasion. In contrast, SENP3 overexpression reversed these effects. In all, results lend novel insights into the regulation of STAT3, which has key roles in bladder cancer progression.	bladder
Distinct Uroplakin II Staining Pattern in Apocrine Breast Carcinoma.	Uroplakin II (UPII) has been shown as a highly specific marker of urothelial carcinoma; however, it can also stain subtypes of apocrine-differentiated breast carcinoma. Given that urothelium and breast epithelium share other common immunohistochemical markers, such as CK7 and GATA3, this can lead to a potential diagnostic pitfall. We stained a cohort of triple-negative breast cancer with UPII. Compared with the diffuse, cytoplasmic staining in urothelial carcinoma, UPII was positive in 38.9% of apocrine carcinoma (7/18) with a course, granular cytoplasmic staining pattern and negative in all nonapocrine triple-negative breast cancer cases. Furthermore, the same staining pattern was present in all apocrine metaplasia of the breast (4/4) and apocrine sweat glands in normal skin (6/6). This distinct subcellular localization of UPII staining in breast carcinoma can offer a potential solution to the above diagnostic pitfall.	bladder
Preoperative sarcopenia and systemic immune-inflammation index can predict response to intravesical Bacillus Calmette-Guerin instillation in patients with non-muscle invasive bladder cancer.	BACKGROUND: To explore the prognostic significance of sarcopenia and systemic immune-inflammation index (SII) for response to intravesical Bacillus Calmette-Guerin (BCG) in patients with intermediate-, and high-risk non-muscle invasive bladder cancer (NMIBC). METHODS: We retrospectively analyzed 183 consecutive patients treated in Qilu hospital of Shandong University for a first diagnosis of intermediate and high risk NMIBC. Using computed tomography scans at the third lumbar vertebra level, we calculated skeletal muscle index (SMI). Sarcopenia was defined as SMI <43 cm(2)/m(2) for males with BMI < 25 kg/m(2), <53 cm(2)/m(2) for males with BMI ≥ 25 kg/m(2), and <41 cm(2)/m(2) for females. The response to intravesical BCG immunotherapy and relapse-free survival (RFS) were analyzed. RESULTS: Compared with BCG responders, BCG non-responders were associated with sarcopenia (P < 0.001), carcinoma in situ (P < 0.001), T1 stage (P < 0.001), multiple tumor (P < 0.001), tumor diameter >=3cm (P < 0.001), and have a significant increase of neutrophil-to-lymphocyte ratio (NLR) (P < 0.001), platelet to lymphocyte ratio (PLR) (P = 0.004), SII (P < 0.001). The area under the ROC curve (AUC) of the BMI, NLR, PLR, and SII for response to intravesical BCG immunotherapy were 0.425, 0.693, 0.631, and 0.702 respectively. Logistic regression analysis demonstrated that sarcopenia and SII were predictors of response to intravesical BCG immunotherapy. The Kaplan-Meier survival analysis showed that the RFS of patients with BCG response, lower SII and no sarcopenia was significantly increased compared with that of patients with BCG non-response, higher SII and sarcopenia, respectively. Subgroup analysis demonstrated that the RFS of patients with high SII and sarcopenia was significantly decreased compared with those with low SII and no sarcopenia in Ta stage subgroup, T1 stage subgroup, non-Cis subgroup, multiple tumor subgroup, single tumor subgroup, tumor diameter≥3cm subgroup and tumor diameter<3cm subgroup, respectively (P < 0.05). However, there was no significant difference in RFS for patients in CIS subgroup (P > 0.05). Multivariate Cox analysis shown that sarcopenia (p=0.005) and high SII (p = 0.003) were significantly associated with poor RFS. CONCLUSIONS: Both sarcopenia and high SII are useful predictors of response to intravesical BCG in intermediate- and high-risk NMIBC patients. Patients with intermediate- and high-risk NMIBC that had sarcopenia or high SII at diagnosis were associated with poor RFS, and the combination of sarcopenia and SII may be a better predictor of RFS.	bladder
CT and clinical features for distinguishing endophytic clear cell renal cell carcinoma from urothelial carcinoma.	PURPOSE We aimed to characterize the clinical and multiphase computed tomography (CT) features of the distinguishing endophytic clear cell renal cell carcinoma (ECCRCC) from endophytic renal urothelial carcinoma (ERUC). METHODS Data from 44 patients (35 men and 9 women) with ECCRCC and 21 patients (17 men and 4 women) with ERUC were retrospectively assessed. The mean patient age was 55 years (48.25- 59.50 years) and 68 years (63.00-73.00 years), respectively. Univariate and multivariate logistic regression analyses were performed to determine independent predictors for ECCRCC and to construct a predictive model that comprised clinical and CT characteristics for the differential diagnosis of ECCRCC and ERUC. Differential diagnostic performance was assessed using the area under the receiver operating characteristic curve (AUC). RESULTS The independent predictors of ECCRCC were heterogeneous enhancement (odds ratio [OR]=0.027, P=.005), hematuria (OR for gross hematuria=53.995, P=.003; OR for microscopic hematuria=31.126, P = .027), and an infiltrative growth pattern (OR=24.301, P = .022). The AUC of the predictive model was 0.938 (P < .001, sensitivity=84.10%, specificity=95.20%), which had a better diagnostic performance than heterogeneous enhancement (AUC=0.766, P=.001, sensitivity=81.82%, specificity=71.43%), hematuria (AUC=0.786, P < .001, sensitivity=81.82%, specificity=66.67%), and infiltrative growth pattern (AUC=0.748, P=.001, sensitivity=90.48%, specificity=59.09%). CONCLUSION The independent predictors, as well as the predictive model of CT and clinical characteristics, may assist in the differential diagnosis of ECCRCC and ERUC and provide useful information for clinical decision-making.	bladder
Genetic variation in the ADIPOQ gene and serum adiponectin increase the risk of bladder cancer.	Bladder cancer (BC) is the 10th most common cancer worldwide. Genetic studies estimated 30% heritability in BC risk. Adiponectin is an adipocytokine that has important roles in the regulation of energy metabolism. Recent evidence suggests dysregulation of adiponectin levels in BC tissues. Serum level of adiponectin is influenced by single nucleotide polymorphisms (SNPs) in the ADIPOQ gene. However, limited evidence is available regarding the association between adiponectin serum levels or SNPs in ADIPOQ and BC risk. This study aimed to assess whether adiponectin serum levels or SNPs in ADIPOQ may modify BC risk. In this case-control study, 114 BC patients were recruited along with 114 controls. Study subjects were genotyped for variations in ADIPOQ SNPs, namely rs17300539, rs266729, rs2241766, and rs1501299. Adiponectin levels were measured from the serum of study subjects. Our analysis showed that the G allele and the GG genotype of rs1501299 were significantly more frequent in BC patients compared to those in the control group (p-value < 0.05). Moreover, two ADIPOQ haplotypes containing the above G allele were associated with increased BC risk (p-value < 0.05). Multivariate analysis showed that increased serum adiponectin, smoking or age were all significant predictors of BC (p-value < 0.05). The data supports use of serum adiponectin and the G allele of rs1501299 SNP in ADIPOQ as potential biomarkers and/or targets in BC. To further validate findings in this study, larger populations of various ethnicities and/or genetic backgrounds are required. More investigations on the functional role of adiponectin in BC will also provide better understanding of potential targeting adiponectin for BC treatment.	bladder
Papillary renal cell neoplasm with reverse polarity: A new subtype of renal tumour with favorable prognosis.	INTRODUCTION: Papillary renal cell neoplasm with reverse polarity (PRNRP) has recently been recognized as an entity separate from the traditional classification of papillary renal cell carcinomas, due to its specific histopathological, immunophenotypic and molecular characteristics, as well as its indolent behavior. MATERIAL AND METHODS: We provide 6 new cases and a review of the literature published until the present time, which comprises a total number of 104 cases. RESULTS: Our PRNRP cases correspond to 5 men and one woman aged between 47 and 91 years. In 5 of the 6 cases, the PRNRP was an incidental finding in nephrectomy specimens. Nephrectomy had been indicated due to the presence of another renal tumor, except for one case, in which surgical intervention was indicated due to PRNRP. Our cases present mass sizes between 2 and 13 mm, as well as papillary histology with a monolayered lining of eosinophilic cells with low-grade nuclei in apical location. Immunohistochemically, they show a constant positivity for GATA3 and negativity for vimentin. KRAS mutations were identified in 50% of our cases. After a follow-up ranging between one and 60 months, 5 of the cases were still alive without recurrences or metastases, and one died from urothelial carcinoma. CONCLUSIONS: Our cases agree with the clinical and pathological characteristics described in the PRNRP cases published to date. With the present study, we provide the first series of national cases corroborating the existence of well-defined and constant diagnostic criteria that allow PRNRP to be considered as a distinctive entity.	bladder
Activation of autophagy triggers mitochondrial loss and changes acetylation profile relevant for mechanotransduction in bladder cancer cells.	Bladder cells are constantly exposed to multiple xenobiotics and bioactive metabolites. In addition to this challenging chemical environment, they are also exposed to shear stress originating from urine and interstitial fluids. Hence, physiological function of bladder cells relies on a high biochemical and biomechanical adaptive competence, which, in turn, is largely supported via autophagy-related mechanisms. As a negative side of this plasticity, bladder cancer cells are known to adapt readily to chemotherapeutic programs. At the molecular level, autophagy was described to support resistance against pharmacological treatments and to contribute to the maintenance of cell structure and metabolic competence. In this study, we enhanced autophagy with rapamycin (1-100 nM) and assessed its effects on the motility of bladder cells, as well as the capability to respond to shear stress. We observed that rapamycin reduced cell migration and the mechanical-induced translocation potential of Krüppel-like transcription factor 2 (KLF2). These effects were accompanied by a rearrangement of cytoskeletal elements and mitochondrial loss. In parallel, intracellular acetylation levels were decreased. Mechanistically, inhibition of the NAD + -dependent deacetylase sirtuin-1 (SIRT1) with nicotinamide (NAM; 0.1-5 mM) restored acetylation levels hampered by rapamycin and cell motility. Taken together, we described the effects of rapamycin on cytoskeletal elements crucial for mechanotransduction and the dependency of these changes on the mitochondrial turnover caused by autophagy activation. Additionally, we could show that targeted metabolic intervention could revert the outcome of autophagy activation, reinforcing the idea that bladder cells can easily adapt to multiple xenobiotics and circumvent in this way the effects of single chemicals.	bladder
Prognostic Signature Development on the Basis of Macrophage Phagocytosis-Mediated Oxidative Phosphorylation in Bladder Cancer.	BACKGROUND: Macrophages are correlated with the occurrence and progression of bladder cancer (BCa). However, few research has focused on the predictive relevance of macrophage phagocytosis-mediated oxidative phosphorylation (MPOP) with BCa overall survival. Herein, we aimed to propose the targeted macrophage control based on MPOP as a treatment method for BCa immunotherapy. METHODS: The mRNA expression data sets and clinical data of bladder cancer originated from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) data set. A systematic study of several GEO data sets found differentially expressed macrophage phagocytosis regulators (DE-MPR) between BCa and normal tissues. To discover overall survival-associated DE-MPR and develop prognostic gene signature with performance validated based on receiver operating curves and Kaplan-Meier curves, researchers used univariate and Lasso Cox regression analysis (ROC). External validation was done with GSE13057 and GSE69795. To clarify its molecular mechanism and immune relevance, GO/KEGG enrichment analysis and tumor immune analysis were used. To find independent bladder cancer prognostic variables, researchers employed multivariate Cox regression analysis. Finally, using TCGA data set, a predictive nomogram was built. RESULTS: In BCa, a four-gene signature of oxidative phosphorylation composed of PTPN6, IKZF3, HDLBP, and EMC1 was found to predict overall survival. With the MPOP feature, the ROC curve showed that TCGA data set and the external validation data set performed better in predicting overall survival than the traditional AJCC stage. The four-gene signature can identify cancers from normal tissue and separate patients into the high-risk and low-risk groups with different overall survival rates. The four MPOP-gene signature was an independent predictive factor for BCa. In predicting overall survival, a nomogram integrating genetic and clinical prognostic variables outperformed AJCC staging. Multiple oncological features and invasion-associated pathways were identified in the high-risk group, which were also correlated with significantly lower levels of immune cell infiltration. CONCLUSION: This paper found the MPOP-feature gene and developed a predictive nomogram capable of accurately predicting bladder cancer overall survival. The above discoveries can contribute to the development of personalized treatments and medical decisions.	bladder